Article
Microbiology
Inma Quilis, Merce Gomar-Alba, Juan Carlos Igual
Summary: The CWI pathway in yeast is activated in response to environmental stresses and morphogenetic processes, regulating cell-wall biosynthesis and actin cytoskeleton during periods of polarized growth. Additionally, it plays a role in delaying cell-cycle progression during cell-surface perturbance, affecting key transitions like Start transcriptional program, DNA replication, and mitosis. The CWI pathway also contributes to the response to genotoxic stress and is connected to the DNA integrity checkpoint, serving as a master brake to stop cell-cycle progression under unfavorable conditions.
Article
Biochemistry & Molecular Biology
Thomas Eekhout, Jose Antonio Pedroza-Garcia, Pooneh Kalhorzadeh, Geert De Jaeger, Lieven De Veylder
Summary: During DNA replication, the WEE1 kinase inhibits cyclin-dependent kinases (CDKs) to safeguard genomic integrity. Wee1 mutant plants are hypersensitive to replication stress due to their inability to respond properly to DNA replication problems. The pol alpha-2 mutant, with a mutated catalytic subunit of DNA polymerase alpha, acts as a suppressor mutant of wee1 by causing instability and interaction loss, leading to a prolonged S-phase.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Sargun Sokhi, Cody W. Lewis, Amirali B. Bukhari, Joanne Hadfield, Edric J. Xiao, Jeremy Fung, Yea Jin Yoon, Wen-Hsin Hsu, Armin M. Gamper, Gordon K. Chan
Summary: Cell cycle checkpoint kinases are important targets for cancer therapy, and their inhibition can induce cell death or increase sensitivity to other genotoxic therapies. In this study, the researchers found that the overexpression of Myt1, a kinase regulating cell cycle progression, confers resistance to inhibitors of other kinases. Elevated Myt1 levels compensate for Cdk1 inhibition and lead to reduced premature mitotic entry and decreased length of mitosis, ultimately increasing cell survival rates. The findings suggest that Myt1 overexpression is a common mechanism by which cancer cells acquire resistance to drugs targeting the G2/M checkpoint.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Plant Sciences
Jose Antonio Pedroza-Garcia, Yanli Xiang, Lieven De Veylder
Summary: Plants utilize DNA damage response pathways to cope with various stresses, involving cell cycle checkpoint mechanisms that either pause the cell cycle for DNA repair or direct cells into differentiation or programmed cell death. Different checkpoint mechanisms control replication processes and G2/M transition, with plant-specific elements such as SOG1 playing a key role. These mechanisms are called upon during development, signaling pathways, and in response to stresses, contributing to plant adaptation to changing environments.
Article
Endocrinology & Metabolism
Mengxue Jiang, Zhijian Kuang, Yaohui He, Yin Cao, Tingyan Yu, Jidong Cheng, Wen Liu, Wei Wang
Summary: This study reveals that SNAPIN plays a crucial role in regulating insulin secretion and beta cell proliferation, with its expression influenced by age and diabetes. The function of SNAPIN is achieved through its impact on cell cycle regulation, suggesting it might be a potential pharmacotherapeutic target for diabetes mellitus.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Vladimir Baran, Alexandra Mayer
Summary: After fertilization, the remodeling of the oocyte and sperm genome is crucial for the successful initiation of mitotic activity in the fertilized oocyte and subsequent proliferation of the early embryo. The specific nature of gene totipotency in early cleavage embryos leads to differences in cell cycle control mechanisms compared to somatic cells. This review focuses on the Chk1 kinase as an important factor in monitoring DNA integrity during early embryogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Genetics & Heredity
Paolo Pizzul, Erika Casari, Marco Gnugnoli, Carlo Rinaldi, Flavio Corallo, Maria Pia Longhese
Summary: This review focuses on the studies performed in Saccharomyces cerevisiae to define the checkpoint concept and identify its players and the mechanisms of activation and deactivation in DNA damage repair.
FRONTIERS IN GENETICS
(2022)
Article
Pharmacology & Pharmacy
Jiayun Xu, Shanshan Sun, Wei Zhang, Jianhong Dong, Changgang Huang, Xin Wang, Mengxian Jia, Hao Yang, Yongjie Wang, Yuanyuan Jiang, Liying Cao, Zhihui Huang
Summary: Irigenin inhibits the proliferation, induces apoptosis, and inhibits migration of GBM cells by suppressing YAP/β-catenin signaling.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Min Zhang, Zhi Dai, Xudong Zhao, Gan Wang, Ren Lai
Summary: The study demonstrated that anticarin beta can effectively suppress proliferation and induce apoptosis in glioma cells, decrease stemness gene expression, induce DNA damage, and eventually lead to apoptosis by regulating oncogene expression. Overall, anticarin beta shows promising potential as an inhibitor for malignant glioma.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biology
Amandine Batte, Sophie C. van der Horst, Mireille Tittel-Elmer, Su Ming Sun, Sushma Sharma, Jolanda van Leeuwen, Andrei Chabes, Haico van Attikum
Summary: MRC1 and CHL1 have distinct roles in the replication stress response, with Mrc1 facilitating the restart of stalled replication forks and Chl1 controlling replication fork rate by regulating dNTP levels. The Chl1 helicase affects RPA-dependent checkpoint activation in response to replication fork arrest.
LIFE SCIENCE ALLIANCE
(2022)
Article
Immunology
Chubei Teng, Yongwei Zhu, Yueshuo Li, Luohuan Dai, Zhouyang Pan, Siyi Wanggou, Xuejun Li
Summary: This study compared the transcriptome characteristics of different groups of glioma samples and identified differentially expressed genes associated with recurrence and progression of low-grade glioma (LGG). Using these genes, a prediction model was established to better identify high-risk and low-risk groups of LGG and provide a foundation for evaluating the risk of LGG recurrence and malignant progression.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Benyu Su, David Lim, Chenyang Qi, Zhongwei Zhang, Junxiao Wang, Fengmei Zhang, Chao Dong, Zhihui Feng
Summary: Cell cycle checkpoint kinases play a crucial role in protecting against replicative stress. Valproic acid (VPA), a histone deacetylase inhibitor, was found to promote breast cancer cell progression into G2/M phase while protecting normal cells by regulating PPP2R2A and Chk1 phosphorylation. The expression levels of PPP2R2A and pChk1 were also associated with patient survival.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Indra A. Shaltiel, Alba Llopis, Melinda Aprelia, Rob Klompmaker, Apostolos Menegakis, Lenno Krenning, Rene H. Medema
Summary: Most Cdks are redundant for normal cell division, but become essential for S-phase entry after DNA damage in G1. In damaged cells, high levels of Cdk4/6 activity are required to inactivate pocket proteins and APC/C-Cdh1 to promote the transition from G1 to S phase.
Article
Cell Biology
I-Lun Hsin, Pei-Ju Wu, Sheau-Chung Tang, Chu-Chyn Ou, Hui-Yi Chang, Huang-Pin Shen, Jiunn-Liang Ko, Po-Hui Wang
Summary: ICG-001 inhibits endometrial cancer by reducing cell viability, cancer stem cell sphere formation, and cell cycle progression, while activating autophagy.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Elena Lo Furno, Isabelle Busseau, Antoine Aze, Claudio Lorenzi, Cima Saghira, Matt C. Danzi, Stephan Zuchner, Domenico Maiorano
Summary: This study reveals the important contribution of translesion DNA synthesis (TLS) to the high mutation rate in early embryos of Xenopus laevis and Drosophila melanogaster. It suggests that TLS may be an unforeseen source of genetic diversity, influencing genome evolution and species adaptation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemical Research Methods
Fengyuan Hu, Jia Lu, Louise S. Matheson, Manuel D. Diaz-Munoz, Alexander Saveliev, Jinbo Xu, Martin Turner
Summary: A computational pipeline named ORFLine was developed to identify and classify smORFs, resulting in the discovery of 5744 unique smORFs in mouse B and T lymphocytes datasets. The study further revealed four novel micropeptides that show evidence of secretion and could potentially serve as mediators of immunoregulatory functions.
Article
Immunology
Elisa Monzon-Casanova, Kirsty J. Bates, Christopher W. J. Smith, Martin Turner
Summary: The study reveals the important roles of polypyrimidine tract binding proteins (PTBP) PTBP1 and PTBP3 in B cells, promoting B cell maturation by regulating gene expression at the posttranscriptional level.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chun Gong, Joanna A. Krupka, Jie Gao, Nicholas F. Grigoropoulos, George Giotopoulos, Ryan Asby, Michael Screen, Zelvera Usheva, Francesco Cucco, Sharon Barrans, Daniel Painter, Nurmahirah Binte Mohammed Zaini, Bjoern Haupl, Susanne Bornelov, Igor Ruiz De Los Mozos, Wei Meng, Peixun Zhou, Alex E. Blain, Sorcha Forde, Jamie Matthews, Michelle Guet Khim Tan, G. A. Amos Burke, Siu Kwan Sze, Philip Beer, Cathy Burton, Peter Campbell, Vikki Rand, Suzanne D. Turner, Jernej Ule, Eve Roman, Reuben Tooze, Thomas Oellerich, Brian J. Huntly, Martin Turner, Ming-Qing Du, Shamith A. Samarajiwa, Daniel J. Hodson
Summary: Loss-of-function mutations in DDX3X can buffer MYC-induced proteotoxic stress, and male B cell lymphomas have the capacity to compensate for this loss by ectopically expressing DDX3Y.
Article
Biochemistry & Molecular Biology
Alison Galloway, Aneesa Kaskar, Dimitrinka Ditsova, Abdelmadjid Atrih, Harunori Yoshikawa, Carolina Gomez-Moreira, Olga Suska, Marcin Warminski, Renata Grzela, Angus Lamond, Edward Darzynkiewicz, Jacek Jemielity, Victoria H. Cowling
Summary: The study reveals that RNMT plays a crucial role in T cell activation by regulating ribosome biogenesis, which is essential for cellular metabolic reprogramming, proliferation, and differentiation. RNMT selectively regulates the expression of mRNAs targeted by the (m7)G-cap binding protein LARP1, impacting ribosome synthesis and translation rates.
NUCLEIC ACIDS RESEARCH
(2021)
Correction
Biochemical Research Methods
Fengyuan Hu, Jia Lu, Louise S. Matheson, Manuel D. Diaz-Munoz, Alexander Saveliev, Martin Turner
Article
Immunology
Vanessa D'Angeli, Elisa Monzon-Casanova, Louise S. Matheson, Ozge Gizlenci, Georg Petkau, Clare Gooding, Rebecca Berrens, Christopher W. J. Smith, Martin Turner
Summary: The RNA-binding protein PTBP1 plays a crucial role in regulating CD8 T-cell activation, controlling alternative splicing of over 400 genes and protecting activated cells from apoptosis.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Georg Petkau, Twm J. Mitchell, Krishnendu Chakraborty, Sarah E. Bell, Vanessa D. Angeli, Louise Matheson, David J. Turner, Alexander Saveliev, Ozge Gizlenci, Fiamma Salerno, Peter D. Katsikis, Martin Turner
Summary: RNA binding proteins ZFP36 and ZFP36L1 limit the rate of differentiation and the potency of activated CD8(+) T cells by directly binding mRNA of transcription factors and cytokines, enforcing dependency on costimulation for full T cell activation and effector differentiation.
NATURE COMMUNICATIONS
(2022)
Article
Biology
David J. Turner, Alexander Saveliev, Fiamma Salerno, Louise S. Matheson, Michael Screen, Hannah Lawson, David Wotherspoon, Kamil R. Kranc, Martin Turner
Summary: In this study, we used a CRISPR/Cas9 knockout screen to identify the roles of RNA binding proteins (RBPs) in the differentiation and survival of antibody secreting plasma cells. Through this screen, we discovered that CSDE1, STRAP, and YTHDF2 promote the accumulation of CD138 + cells, while EIF3K, EIF3L, and components of the CCR4-NOT complex inhibit CD138 + cell accumulation. Additionally, YTHDF2-deficient plasma cells were found to fail in accumulation in chimeric mouse models.
Article
Multidisciplinary Sciences
Louise S. Matheson, Georg Petkau, Beatriz Saenz-Narciso, Vanessa D'Angeli, Jessica McHugh, Rebecca Newman, Haydn Munford, James West, Krishnendu Chakraborty, Jennie Roberts, Sebastian Lukasiak, Manuel D. Diaz-Munoz, Sarah E. Bell, Sarah Dimeloe, Martin Turner
Summary: The ZFP36 family of RNA-binding proteins directly limit gene expression to repress metabolism and differentiation in CD4(+) T cells, specifically targeting transcription factors and transcripts encoding rate-limiting enzymes. Deficiency of ZFP36 and ZFP36L1 result in increased cellular glutamine content and activation of anabolic processes. Glutamine and alpha-ketoglutarate may serve as limiting factors for the acquisition of cytotoxic CD4(+) T cell fate.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Ines C. Osma-Garcia, Dunja Capitan-Sobrino, Mailys Mouysset, Yann Aubert, Orlane Maloudi, Martin Turner, Manuel D. Diaz-Munoz
Summary: This study reveals the importance of tight regulation of RNA splicing by TIA1 and TIAL1 for the expression of integrative transcriptional programs that control DNA damage sensing and repair during B cell development.
Review
Biochemistry & Molecular Biology
Martin Turner
Summary: Pre-existing but untranslated or 'poised' mRNA serves as a rapid response mechanism and a safeguard in immune cells. The molecular mechanisms that control the translation of poised mRNA have yet to be fully understood, but they likely involve intrinsic properties of the mRNA and its interactions with trans-acting factors. This article discusses potential regulatory mechanisms.
Article
Cell Biology
Andrew C. Cicchetto, Elsie C. Jacobson, Hannah Sunshine, Blake R. Wilde, Abigail S. Krall, Kelsey E. Jarrett, Leslie Sedgeman, Martin Turner, Kathrin Plath, M. Luisa Iruela-Arispe, Thomas Q. de Aguiar Vallim, Heather R. Christofk
Summary: Cellular metabolism is regulated by growth factor signaling, and this study identifies the ZFP36/L1/L2 family of RNA-binding proteins and mRNA decay factors as key regulators of metabolic rewiring downstream of acute growth factor signaling. The researchers found that ZFP36 directly promotes the degradation of multiple metabolic enzyme and nutrient transporter mRNAs, including those encoding rate-limiting steps in metabolic pathways. They also demonstrated that ZFP36-mediated mRNA decay affects the expression and activity of Enolase 2 (Eno2), and plays a role in VEGF-stimulated developmental retinal angiogenesis.
Article
Biology
Ana Martinez-Riano, Pilar Delgado, Rut Tercero, Sara Barrero, Pilar Mendoza, Clara L. L. Oeste, David Abia, Elena Rodriguez-Bovolenta, Martin Turner, Balbino Alarcon
Summary: Researchers have developed an antigen-specific in vitro germinal center system using just two cell types, B cells and CD4+ T cells, to investigate the immune response and T cell help in the production of class-switched high affinity immunoglobulins. The lack of an antigen-specific in vitro germinal center system has been a major obstacle in understanding the mechanisms of B cell:T cell cooperation. By using this system, the researchers demonstrated that T cells provide directional help to antigen-presenting B cells, but not bystander B cells, leading to the generation of class-switched antibodies.
COMMUNICATIONS BIOLOGY
(2023)
Meeting Abstract
Immunology
G. Petkau, T. J. Mitchell, K. Chakraborty, S. E. Bell, V. D'Angeli, L. Matheson, D. J. Turner, A. Saveliev, O. Gizlenci, F. Salerno, P. D. Katsikis, M. Turner
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Meeting Abstract
Immunology
Ines C. Osma Garcia, Dunja Capitan Sobrino, Mailys Mouysset, Sarah E. Bell, Manuel Lebeurrier, Martin Turner, Manuel D. Diaz Munoz
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)